Recent studies suggest that the ventral medulla oblongata regulates sympathetic efferent activity to the cardiovascular system. Anatomical studies show that fibers originating in the ventral medulla (i.e., nucleus interfascicularis hypoglossi and nucleus reticularis gigantocellularis, pars Alpha) innervate the intermediolateral cell column (IML), the site of origin of pregaglionic sympathetic neurons. However, the neurotransmitter(s) contained in this projection to the IML and their role in mediating the cardiovascular effects elicited from the ventral medulla are not well defined. Ventral medullary neurons contain serotonin, substance P, or TRH; some contain more than one of these putative neurotransmitters. However, only serotonergic neurons are known to project to the IML ant their function is not known. Preliminary studies suggest that substance P neurons also project from the ventral medulla to the IML and that they are not dual transmitter substance P-serotonergic neurons. In addition, we have found that the pharmacological sensitivity of the ventral medulla of the rat is similar to the cat and therefore the rat appears to be a good model in which to correlate neuroanatomical, neurochemical, and neuropharmacological studies of this area. The proposed experiments are intended to further characterize the rat as a model to study the ventral medulla. We will then study the neuroanatomy and neurochemistry of efferent pathways to the IML with a focus on serotonin, substance P, and TRH. We want to provide further neurochemical characterization of the descending neurons, specific localization of cell bodies in correlation with their neurotransmitters and projection site in the spinal cord, and to study interaction(s) between descending transmitter systems. Finally, we will determine the function of these descending neurotransmitter systems in transmitting the cardiovascular effects mediated by the ventral medulla. We will use in vivo physiological and pharmacological techniques, autoradiography, and lesion and retrograde transport techniques combined with radioimmunoassay and immunocytochemistry. These studies will provide information on the neurochemistry, neuroanatomy, and the functional role of descending projections from the ventral medulla. In addition, they will enhance our knowledge of CNS mechanisms important for the control of the cardiovascular system.